1. Technical Field
This document provides methods and materials relating to isolated vaccinia virus-derived polypeptides. For example, this document relates to specific and naturally processed and HLA presented vaccinia virus-derived polypeptides isolated from a membrane polypeptide such as B5R, L1R, A33R, and A27L of vaccinia virus, a member of the Orthopoxvirus family. This document provides methods and materials for generating a vaccine for preventing or treating an Orthopoxvirus infection that induces a protective therapeutic immune response. The vaccines can include one or more of the isolated vaccinia virus polypeptides provided herein. In some cases, this document provides kits related to the use of vaccinia virus polypeptides.
2. Background Information
Polypeptide-based vaccines use small polypeptide sequences derived from target proteins as epitopes to provoke an immune reaction. These vaccines are a result of an improved understanding of the molecular basis of epitope recognition, thereby permitting the development of rationally designed, epitope-specific vaccines based on motifs demonstrated to bind to human class I (HLA I) or class II (HLA II) major histocompatibility complex (MHC) molecules. Of particular interest has been the discovery of epitopes that are specifically recognized by T cells for prophylaxis and treatment of infectious diseases.
Over the centuries, naturally occurring smallpox, with its case-fatality rate of 30 percent or more and its ability to spread in any climate and season, has been universally feared as one of the most devastating of all the infectious diseases. The use of vaccinia virus as a vaccine enabled the global eradication of naturally occurring smallpox. The last naturally occurring case of smallpox occurred in Somalia in 1977. In May 1980, the World Health Assembly certified that the world was free of naturally occurring smallpox. Routine vaccination against smallpox in the United States ended in 1971, and except for some soldiers and laboratory workers, no one has been vaccinated since 1983. However, terrorist activities in the early 21st century as well as imported outbreaks of monkeypox (a member of the Orthopox virus family) in the USA, spurred renewed interest in biodefense countermeasures for these public health threats (Artenstein et al., Expert Rev. Vaccines, 7:1225-1237 (2008) and Giulio et al., Lancet Infect. Dis., 4:15-25 (2004)).